Retinoblastoma (RB) is a childhood ocular tumor that can lead to blindness and death if not diagnosed early. Currently, the management of RB patients depends on tumor stage at diagnosis. Enucleation is the therapeutic option for those with large unilateral tumors and no family history of disease (60-70% of all RB patients). In a subset of these patients, enucleation is followed by adjuvant chemotherapy to reduce the risks of tumor recurrence and metastasis. For bilateral RB cases, enucleation of the most affected eye is followed by systemic chemotherapy to the other eye. Despite these therapies, 30% of bilateral and 15% of unilateral (15%) cases, experience tumor recurrence defined by formation of new tumors within the first 1 to 3 years after diagnosis and enucleation. The goal of this project is to identify molecular markers associated with tumor recurrence risk. We hypothesize that a comprehensive study of genomic instability within RB tumors by using whole genome SNP (single nucleotide polymorphism) based chromosomal copy number analysis and correlating this information with microarray based gene expression studies, will help to identify molecular markers that will be informative of tumor biology and recurrence risk. To rigorously test this hypothesis, we propose a set of complementary specific aims, which will make use of genomic techniques to analyze RB tumor samples with associated clinical data. Specific Aim 1 To obtain a profile of loss and gain of chromosomal regions sampled from the whole genome of a RB tumor that can be used to predict recurrence of the disease. Specific Aim 2 To obtain the profile of gene expression of RB tumors that can identify molecular markers that will predict the risk of recurrence of the disease. Specific Aim 3 To combine the data obtained from Aims 1 and 2 to build a molecular classifier for RB recurrence. The outcome of this project will be high resolution whole genome profiles of a set of well-annotated RB tumors. This data can be analyzed to give a better understanding of the underlying biology of RB tumorigenesis. In many other types of cancer, these profiles have been used to identify class specific molecular signatures that can predict risk of tumor recurrence. The identification of molecular signatures will translate to improved management of future pediatric patients with RB, save the vision and change the quality of life of affected children and their families. Retinoblastoma (RB) is a childhood ocular tumor that can lead to blindness and death if not diagnosed early. The objective of this project is to facilitate the management of patients with RB, based on a better understanding of the molecular etiology of RB tumor initiation, progression and recurrence risk. To this end we will utilize new powerful high- resolution genomic profiling technologies to measure both chromosomal aberrations and gene expression levels in different classes of RB tumors. This will allow us to identify molecular signatures associated with risk of RB recurrence. [unreadable] [unreadable] [unreadable] [unreadable]